Genetic Polymorphism of Glutathione S-transferase T1 (GSTT1) and QT-Interval in Schizophrenia Patients

Abstract

Several antipsychotic agents are known to prolong the QT interval in a dose-dependent manner. The antipsychotic drugs are substrates of the phase I of biotransformation enzymes of cytochrome P450. In order to find the possible influence of polymorphism of GSTT1 (a member of class theta glutathione S-transferase) on rate-corrected QT interval (QTc) of schizophrenia patients, the present study was done. Forty-three schizophrenia in-patients participated in the study. The patients were diagnosed as chronic schizophrenia according to structured clinical interview using SCID-I (clinician version) to confirm and document DSM-IV diagnosis. Measurements of QT and RR intervals were recorded using a magnifying grid on lead II. The QTc was calculated according to Bazett's formula. Polymerase chain reaction-based method was used in order to determine the GSTT1 genotypes. Based on the fitted model of multiple linear regression analysis, QTc decreased in persons with positive GSTT1 genotype in comparison with the null genotype (beta = -0.328, t = -2.346, p = 0.024). Active genotype of GSTT1 decreased the QTc. Also, QTc was significantly associated with smoking status; it was decreased in smokers compared with nonsmokers (beta = -0.372, t = -2.372, p = 0.014).

Association between QTc of patients with schizophrenia and five genetic polymorphisms of GSTZ1 and XRCC1

“…We have previously found that the GSTT1 polymorphism was associated with the risk of schizophrenia18 and QTc in these patients 17. The present results indicate that GSTZ1 , which is another detoxifying glutathione S-transferase (GST) enzyme, is not associated with QTc in patients treated with antipsychotic drugs.…”

“…It has also been shown that the QTc interval in patients with schizophrenia is correlated with the GSTT1 polymorphism 17. In the present study the association between QTc in patients with schizophrenia and polymorphisms of XRCC1 and GSTZ1 was investigated.…”

QTc prolongation in patients with schizophrenia taking antipsychotics: Prevalence and risk factors

“…To our knowledge, very few studies evaluated the effect of smoking on QTc prolongation (Bahaoddini et al, 2009; Ramos-Ríos et al, 2010). Bahaoddini et al conducted a multiple linear regression and reported an association between smoking and QTc prolongation (Bahaoddini et al, 2009). A cross-sectional study performed by Ramos-Ríos in an Italy psychiatric hospital proved this point (Ramos-Ríos et al, 2010).…”

“…Despite these findings, it remained unclear whether antipsychotic drugs consistently led to QTc prolongation. In addition, gender (Haddad and Sharma, 2007; Lin et al, 2004), age (Haddad and Sharma, 2007; He et al, 2022), comorbidity of cardiovascular disease (De Yang et al, 2011; Nielsen et al, 2014), smoking (Bahaoddini et al, 2009; Ramos-Ríos et al, 2010), and high-density lipoprotein/low-density lipoprotein (HDL/LDL) level (Del Giorno et al, 2019) might affect QTc interval, although there is still debate about the risk of these associated factors. Given that patients with schizophrenia have a higher rate of premature death when not treated in a timely fashion (Smith et al, 2013), it is essential to identify the possible risk factors for QTc prolongation.…”

Genetic Variations in Human Glutathione Transferase Enzymes: Significance for Pharmacology and Toxicology

“…(ii) Publication bias : studies which find significant associations are more likely to be published than studies which find no association. The recent HuGE meta-analysis of asthma studies [94] noted “clear absence of small studies with negative results, suggesting the presence of publication bias.” (iii) Small sample size : published studies of the GSTT1 and GSTM1 polymorphisms include samples as small as 34 patients with chronic obstructive pulmonary disease [100], 51 liver transplant recipients [101], and 43 schizophrenia patients [102], and such small samples are unlikely to yield reliable data. (iv) Lack of clear biological rationale : is it reasonable to expect that the presence of a non-null GSTT1 gene is associated with, for example, significantly better response to the surgical correction of an enlarged scrotal vein [103]?…”